Dexanabinol (HU-211) is a synthetic cannabinoid derivative, but it does not act as a cannabinoid receptor agonist. Dexanabinol is the (−) enantiomer of 1,1 dimethyl heptyl-(3S,4S)-7-hydroxy-Δ6-tetrahydrocannabinol also known as (6aS,10aS) 9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol and has recently become of interest due to its activity as anticancer therapy. It is the “unnatural” enantiomer of the potent cannabinoid agonist HU-210.
The (+) enantiomer, HU-210, is (6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol 1, which is known as a potent synthetic cannabinoid.

The synthetic route to high enantiomerically pure dexanabinol is described in US Patent application 2004/0110827.
The synthesis described therein (but not including (R)-verbenone) is shown schematically in Scheme 1 below:
In the known process for the synthesis of dexanabinol, a key compound is (+)-4-hydroxymyrtenol pivalate, which is coupled with dimethyheptyl resorcinol to produce dexanabinol.
However, the known synthetic route is disadvantageous in that, inter alia, stage 1 of the process requires the oxidation of (+)-α-pinene with t-butylhydroperoxide in the presence of selenium dioxide, producing a mixture of (+) myrtenol ((1R)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-methanol) and (+) myrtenal.

The use of selenium is very undesirable as it requires removing from the end product. Furthermore, the use of selenium dioxide requires the employment of dedicated plant equipment in order to avoid contamination. In addition, the disclosed synthetic route only produces a moderate yield.
Furthermore, the process requires allylic carbon oxidation at the internal ring carbon of (+)-myrtenol pivalate, employing chromium oxide based conditions to generate (+)-oxomyrtenol pivalate. However, the oxidation step with chromium oxide is very low yielding, ˜20% and the (+)-oxomyrtenol pivalate produced is difficult to purify.
Thus, there is a need for an improved synthetic process for the manufacture of cannabinoids, such as dexanabinol and HU-210, which avoids the use of undesirable agents, such as selenium dioxide and/or chromium oxide.
We have now found a novel synthetic route for cannabinoids which overcomes or mitigates the aforementioned disadvantages and/or provides and improved yield of the desired cannabinoid, e.g. dexanabinol and HU-210.